Single-cell transcriptomic analysis identifies the conversion of zebrafish Etv2-deficient vascular progenitors into skeletal muscle

Brendan Chestnut; Satish Casie Chetty; Andrew L. Koenig; Saulius Sumanas

doi:10.1038/s41467-020-16515-y

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Single-cell transcriptomic analysis identifies the conversion of zebrafish Etv2-deficient vascular progenitors into skeletal muscle

Journal article

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Single-cell transcriptomic analysis identifies the conversion of zebrafish Etv2-deficient vascular progenitors into skeletal muscle

Brendan Chestnut, Satish Casie Chetty, Andrew L. Koenig and Saulius Sumanas

Nature communications, Vol.11(1), pp.2796-16

06/03/2020

DOI: 10.1038/s41467-020-16515-y

PMID: 32493965

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Abstract

Cell fate decisions involved in vascular and hematopoietic embryonic development are still poorly understood. An ETS transcription factor Etv2 functions as an evolutionarily conserved master regulator of vasculogenesis. Here we report a single-cell transcriptomic analysis of hematovascular development in wild-type and etv2 mutant zebrafish embryos. Distinct transcriptional signatures of different types of hematopoietic and vascular progenitors are identified using an etv2(ci32Gt) gene trap line, in which the Gal4 transcriptional activator is integrated into the etv2 gene locus. We observe a cell population with a skeletal muscle signature in etv2-deficient embryos. We demonstrate that multiple etv2(ci32Gt); UAS:GFP cells differentiate as skeletal muscle cells instead of contributing to vasculature in etv2-deficient embryos. Wnt and FGF signaling promote the differentiation of these putative multipotent etv2 progenitor cells into skeletal muscle cells. We conclude that etv2 actively represses muscle differentiation in vascular progenitors, thus restricting these cells to a vascular endothelial fate. The signals restricting specification of vascular progenitors are unclear. Here, the authors use scRNAseq to identify transitional steps during blood and vascular development in zebrafish and identify Etv2 as repressing skeletal muscle differentiation in vascular progenitors.

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Details

Title: Subtitle: Single-cell transcriptomic analysis identifies the conversion of zebrafish Etv2-deficient vascular progenitors into skeletal muscle
Creators: Brendan Chestnut - Cincinnati Children's Hospital Medical Center
Satish Casie Chetty - Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA
Andrew L. Koenig - Cincinnati Children's Hospital Medical Center
Saulius Sumanas - Cincinnati Children's Hospital Medical Center
Resource Type: Journal article
Publication Details: Nature communications, Vol.11(1), pp.2796-16
DOI: 10.1038/s41467-020-16515-y
PMID: 32493965
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: NATURE PORTFOLIO
Number of pages: 16
Grant note: F31 HL135986 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01 HL134815; R21 AI128445 / National Insitute of Health: NIH
Language: English
Date published: 06/03/2020
Academic Unit: Stead Family Department of Pediatrics
Record Identifier: 9985161354602771

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